IRB Study Number 25-572
Status Recruiting
Phase Phase 2
Locations Cleveland Clinic Main Campus, Cleveland Clinic Weston Hospital
Institute Taussig Cancer Institute
Description
Primary Objectives
To determine the recommended dose for Part 2 (RP2D) and to assess the efficacy of WSD0922-FU by assessment of ORR by RECIST v1.1.
Secondary Objectives
To further assess the efficacy of WSD0922-FU in terms of:
Progression Free Survival (PFS)
Duration of Response (DoR)
Disease Control Rate (DCR)
Change in Tumor Size
Overall Survival (OS)
To assess the effect of WSD0922-FU on patients’ disease-related symptoms and health related quality of life (HRQoL).
To characterize the PK of WSD0922-FU and metabolites in patients receiving WSD0922-FU.
Inclusion Criteria
Provision of signed and dated, written informed consent prior to any study-specific procedures, sampling, and analyses.
Male or female aged ≥18 years old.
Histological or cytological confirmation diagnosis of NSCLC.
Locally advanced or metastatic NSCLC, not amenable to curative surgery or radiotherapy.
Evidence of radiological disease progression while on a previous continuous treatment with first line third generation of EGFR TKI (i.e., Osimertinib as first-line treatment for advanced/metastatic disease). In addition, one line of chemotherapy (with or without immunotherapy) as second line may be given. All patients must have documented radiological progression on the last treatment administered prior to enrolling in the study.
Documented EGFR mutation (at any time since the initial diagnosis of NSCLC) known to be associated with EGFR TKI sensitivity.
Patients must have confirmation of C797S mutation positive status from either a plasma sample or a tissue biopsy sample taken after documented disease progression on the most recent treatment regimen (irrespective of whether this is a third generation of EGFR TKI (i.e., Osimertinib) or chemotherapy at a local laboratory using next-generation sequencing (NGS) (Note: results from a prior assessment performed as per standard of care is also acceptable). Patients must have central laboratory confirmation, in addition to local testing, of tumor C797S mutation positive status from a liquid biopsy (tissue biopsy to also be collected if available for patients where the local laboratory test was done on tissue) taken after documented disease progression on the most recent treatment regimen (irrespective of whether this is a third generation of EGFR tyrosine kinase inhibitor (i.e., Osimertinib) or chemotherapy.
Performance status:
ECOG 0-1 with no deterioration over the previous 2 weeks and a minimum life expectancy of 12 weeks.
At least one lesion, not previously irradiated and not chosen for biopsy during the study, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) which is suitable for accurate repeated measurements. If only one measurable lesion exists, it is acceptable to be used as long as it has not been previously irradiated, and baseline tumor assessment scans are done at least 14 days after the screening biopsy is performed.
Females should be using adequate contraceptive measures, should not be breast feeding, and must have a negative pregnancy test prior to start of dosing if of childbearing potential or must have evidence of non-childbearing potential by fulfilling one of the following criteria at screening:
Post-menopausal defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments
Women under 50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH) levels in the post-menopausal range for the institution
Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy, but not tubal ligation.
Male patients should be willing to use barrier contraception i.e., condoms.
Patient must be stable on no more than 2 mg of dexamethasone (or equivalent steroids) per day. Steroid dose should not be adjusted during Cycle 1 of therapy.
Exclusion Criteria
- Treatment with any of the following:
• Treatment with more than 2 prior lines of treatment for advanced NSCLC
• Treatment with Osimertinib within 8 days or approximately 5x half-life, whichever is the longer, of the first dose of study treatment. (If sufficient washout time has not occurred due to schedule or PK properties, an alternative appropriate washout time based on known duration and time to reversibility of drug related AEs could be agreed upon by Wayshine and the investigator)
• Any investigational agents or other anticancer drugs from a previous treatment regimen or clinical study within 14 days of the first dose of study treatment.
• Previous treatment with WSD0922-FU, or a 4th generation EGFR TKI
• Prior neo-adjuvant or adjuvant chemotherapy treatment within 6 months of starting first EGFR TKI treatment. (While neo-adjuvant and adjuvant chemotherapy more than 6 months ago is allowed, if the recurrence post adjuvant is less than 6 months, the subsequent treatment would be considered second line, rather than first line.)
• Major surgery (excluding placement of vascular access) within 4 weeks
• Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks
• Patients currently receiving (or unable to stop use at least 1 week prior to receiving the first dose of WSD0922-FU) medications or herbal supplements known to be potent inhibitors or inducers of CYP3A4
• Concurrent enrollment in another clinical study, unless it is an observational (noninterventional) clinical study or during the follow-up period of an interventional study
Any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of starting study treatment with the exception of alopecia (any grade), pigmentation (any grade), and peripheral neuropathy (Grade ≤2).
Symptomatic brain complications that require urgent neurosurgical or medical (e.g., mannitol) intervention.
Anticonvulsants and corticosteroids (as long as these do not exceed 2 mg of dexamethasone [or equivalent steroids] per day) are permitted for patients with brain metastasis. Patients with brain metastasis who require radiotherapy are also allowed to participate in the study if stable and radiotherapy was within 2 weeks before study drug treatment.
Leptomeningeal metastasis.
Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the investigator’s opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol, or active infection including hepatitis B, hepatitis C, and human immunodeficiency virus (HIV). Screening for chronic conditions is not required.
Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of WSD0922-FU.
Any of the following cardiac criteria:
• Mean resting corrected QT interval (QTc) > 480 msec, obtained from ECGs
• Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval > 250 msec
• Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives, or any concomitant medication known to prolong the QT interval.
Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
• Absolute neutrophil count < 1.5 x 109/L
• Platelet count < 100 x 109/L
• Hemoglobin < 9.0 g/dL
• ALT > 2.5 times the upper limit of normal (ULN) if no demonstrable liver metastases or > 5 times ULN in the presence of liver metastases
• AST > 2.5 times ULN if no demonstrable liver metastases or > 5 times ULN in the presence of liver metastases
• Total bilirubin > 1.5 times ULN if no liver metastases or > 3 times ULN in the presence of documented Gilbert’s Syndrome (unconjugated hyperbilirubinemia) or liver metastases
• Estimated glomerular filtration rate (eGFR) < 60 mL/minute
History of hypersensitivity of WSD0922-FU (or drugs with a similar chemical structure or class to WSD0922-FU).
Males and females of reproductive potential who are not using an effective method of birth control and females who are pregnant or breastfeeding or have a positive (urine or serum) pregnancy test prior to study entry.
Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements.
Patients confirmed to have EGFR T790M, cMet amplification, or EGFR exon 20 insertion mutation.
Known intracranial hemorrhage which is unrelated to tumor.
Seizures requiring a change in anti-epileptic medications (addition of new anti-epileptic or increase in dose) ≤ 2 weeks of study start.
Patient must not take enzyme-inducing anticonvulsants treatment for at least 2 weeks before study enrollment. Patients on enzyme-inducing anticonvulsants will be changed to non-enzyme-inducing anticonvulsants. Drug-drug interactions with proton pump inhibitor (PPI), H2 blockers, or antacids have not been assessed, therefore it is suggested to avoid taking those drugs together with WSD0922-FU (refer to Appendix F for a list of prohibited medications).
In addition, the following is considered a criterion for exclusion from the exploratory genetic research:
Previous allogenic bone marrow transplant.
Non-leukocyte-depleted whole blood transfusion within 120 days of the date of the genetic sample collection.
